Professor of Otolaryngology - Head and Neck Surgery (Pediatrics) at the Stanford University Medical Center and, by courtesy, of Pediatrics at the Lucile Salter Packard Children's Hospital

Otolaryngology - Head & Neck Surgery Divisions

Bio

Bio

Dr. Chang's clinical practice is based at the Lucile Packard Children's Hospital, and is focused on Pediatric Otology. He has specific clinical interests in congenital hearing loss, congenital ear anomalies, microtia and atresia reconstruction, and pediatric cochlear implantation. His research interests are also in hearing loss, and include neonatal hearing screening, genetics of hearing loss, otoacoustic emissions, auditory physiology, and ototoxicity. He is actively involved in several human clinical trials looking at the prevention of cisplatin ototoxicity that may drastically decrease the number of children developing hearing loss after chemotherapy, and also presented the Chang Ototoxicity Scale in Journal of Clinical Oncology. His current research interests include the radiologic evaluation of congenital inner ear anomalies, and the analysis of how Connexin-based mutations can alter management of infants with congenital hearing loss.

Dr. Chang received his B.A. magna cum laude at Brown University, graduating Phi Beta Kappa. He continued there for his M.D. degree, receiving the Henry Randall Prize and the Sigma Xi Award. He completed his Otolaryngology residency in Seattle, at the University of Washington. This was followed by a fellowship in Pediatric Otolaryngology at the Children's Hospital of Pittsburgh. He joined the faculty at Stanford University in 2000.

Research & Scholarship

Current Research and Scholarly Interests

Dr. Chang's research interests include congenital hearing loss, neonatal hearing screening, genetics of hearing loss, otoacoustic emissions, auditory physiology, and ototoxicity. He is actively involved in several human clinical trials looking at the prevention of cisplatin ototoxicity that may drastically decrease the number of children developing hearing loss after chemotherapy, and also presented the Chang Ototoxicity Scale in Journal of Clinical Oncology. His current research interests include the radiologic evaluation of congenital inner ear anomalies, and the analysis of how Connexin-based mutations can alter management of infants with congenital hearing loss.

Clinical Trials

Study of OTO-104 in Subjects at Risk From Cisplatin-Induced Hearing LossNot Recruiting

This is a multicenter, Phase 2 study to assess the feasibility, safety and efficacy of
OTO-104 given by intratympanic administration in subjects at risk for ototoxicity from
cisplatin chemotherapy regimens in the treatment of cancer.

Stanford is currently not accepting patients for this trial.For more information, please contact Cancer Clinical Trials Office (CCTO), 650-498-7061.

All neonates, ages 0 to 4 months, presenting to LPCH pediatric ENT clinic for airway
difficulties or stridor will be screened for inclusion. As is consistent with an acceptable
standard of medical care, these children will undergo a flexible nasal endoscopic exam to
make the diagnosis of laryngomalacia, as well as be weighed and a breastfeeding history
taken. If laryngomalacia is present, the study staff with then administer the Infant
Gastroesophageal Reflux Questionnaire (IGERQ) and an airway symptoms questionnaire (ASQ).
Those babies with an IGERQ score of less than sixteen (no more than mild reflux) and an ASQ
score greater than six will be eligible for randomization. The patient will then be randomly
placed in the control group (placebo) or the intervention group (ranitidine 2mg/kg every 12
hours or famotidine 0.5 mg/kg daily). Patients will stay on medication for a minimum of 6
months, or until symptoms resolve. Patients will be seen in follow up at 1, 2, 3, 4, 5, 6, 8
and 10 months. At which time I-GERQ, ASQ and weights will be taken. The primary outcome
measure will be the time for the ASQ score to drop to normal on ranitidine or famotidine
versus placebo.
A secondary outcome will be weight gain in percentile. If the patient's I-GERQ score goes
above 16 at any time in the study, the patient will be crossed over to the treatment arm and
started on medical treatment.

Stanford is currently not accepting patients for this trial.For more information, please contact Lorene Nelson, PhD, 650-723-6854.

Abstract

Hearing loss (HL) is common in childhood cancer survivors exposed to platinum chemotherapy and/or cranial radiation and can severely impact quality of life. Early detection and appropriate management can mitigate academic, speech, language, social, and psychological morbidity resulting from hearing deficits. This review is targeted as a resource for providers involved in aftercare of childhood cancers. The goal is to promote early identification of survivors at-risk for HL, appropriate evaluation and interpretation of diagnostic tests, timely referral to an audiologist when indicated, and to increase knowledge of current therapeutic options.

Abstract

Patients treated with cranial radiation therapy (RT) are at risk for sensorineural hearing loss (SNHL). Although SNHL is often characterized as a delayed consequence of anticancer therapy, longitudinal reports of SNHL in childhood cancer survivors treated with contemporary RT are limited. We report the incidence, onset, severity, and long-term trajectory of SNHL among children receiving RT. Potential risk factors for SNHL were also identified.Serial audiologic testing was conducted on 235 pediatric patients who were treated with conformal or intensity-modulated RT as part of an institutional phase II trial for localized primary brain tumors, including craniopharyngioma, ependymoma, and juvenile pilocytic astrocytoma. All but one patient had measurable cochlear radiation dose (CRD) greater than 0 Gy. The median follow-up from RT initiation to latest audiogram was 9 years with a median of 11 post-RT audiograms per patient. Audiograms were classified by the Chang Ototoxicity Grading Scale. Progression was defined by an increase in Chang grade from SNHL onset to the most recent evaluation.At last evaluation, SNHL was prevalent in 14% of patients: 2.1% had mild and 11.9% had significant SNHL requiring hearing aids. Median time from RT to SNHL onset was 3.6 years (range, 0.4 to 13.2 years). Among 29 patients with follow-up evaluations after SNHL onset, 65.5% experienced continued decline in hearing sensitivity in either ear and 34.5% had no change. Younger age at RT initiation (hazard ratio [HR], 2.32; 95% CI, 1.21 to 4.46), higher CRD (HR, 1.07; 95% CI, 1.03 to 1.11), and cerebrospinal fluid shunting (HR, 2.02; 95% CI, 1.07 to 3.78) were associated with SNHL.SNHL is a late effect of RT that likely worsens over time. Long-term audiologic follow-up for a minimum of 10 years post-RT is recommended.

Abstract

A large-scale review is needed to characterize the rates of airway, respiratory, and cardiovascular complications after pediatric tonsillectomy and adenoidectomy (T&A) for inpatient and ambulatory cohorts.To identify risk factors for postoperative complications stratified by age and operative facility type among children undergoing T&A.This retrospective review included 115?214 children undergoing T&A in hospitals, hospital-based facilities (HBF), and free-standing facilities (FSF) in California from January 1, 2005, to December 31, 2010. The analysis used the State of California Office of Statewide Health Planning and Development private inpatient data and Emergency Department and Ambulatory Surgery public data. Inpatient (n?=?18?622) and ambulatory (n?=?96?592) cohorts were identified by codes from the International Classification of Diseases, Ninth Revision, and Current Procedural Terminology. Data were collected from September 2011 to March 2012 and analyzed from March through May 2012.Rates of airway, respiratory, and cardiovascular complications.A total of 18?622 inpatients (51% male; 49% female; mean age, 5.4 [range, 0-17] years) and 96?592 ambulatory patients (37% male; 35% female; 28%, masked; mean age, 7.6 [range, 0-17] years) underwent analysis. The ratio of ambulatory to inpatient procedures was 5:1. Inpatients demonstrated more comorbidities (?8,compared with ?4 for HBF and ?3 for FSF patients) and, in general, their complication rates were 2 to 5 times higher (seen in 1% to 12% of patients) than those in HBFs (0.2% to 5%), and more than 10 times higher than those in the FSFs (0% to 0.38%), with rates varying markedly by age range and facility type. Tonsillectomy and adenoidectomy was associated with increased risk for all complication types in both settings, reaching an odds ratio of 8.5 (95% CI, 6.6-11.1) for respiratory complications in the ambulatory setting. Inpatients aged 0 to 9 years experienced higher rates of airway and respiratory complications, peaking at an odds ratio of 7.5 (95% CI, 3.1-18.2) for airway complications in the group aged 0 to 11 months.Large numbers of pediatric patients undergo T&A in ambulatory settings despite higher rates of complications in younger patients and patients with more comorbidities. Fortunately, a high percentage of these patients has been appropriately triaged to the inpatient setting. Further research is needed to elucidate the subgroups that warrant postoperative hospitalization.

A modified technique for firm elevation of the reconstructed auricle.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery2016

Abstract

Reconstruction of the external ear for microtia remains one of the most challenging clinical problems in reconstructive surgery. Whether the reconstructive effort replicates a normal ear relates to making a delicate ear cartilage framework and achieving a firm projection of the constructed auricle. In this study, we present a new technique to create a firm elevation. 46 patients with congenital microtia, 30 male and 16 female, are included in this series. We used a modified Nagata's two-stage technique. In the second stage, instead of using a temporoparietal fascial flap to wrap a cartilage wedge, we developed a new technique using the retroauricular fascial flap wrapping a porous polyethylene (Medpor) wedge as the strut. None of the patients demonstrated any necrosis for the implanted auricle and grafted skin. None of the patients had postoperative exposure of the porous polyethylene wedge. The height of the protrusion for point 1 (the protrusion at superaurale level) and point 2 (the inferior end of the helix, where it connects with the lobule) ranged from 1.1 to 1.6 cm with the median of 1.23 cm, and from 0.8 to 1.1 cm with the median of 0.93 cm, respectively. The advantages of this technique are safe, practical and straightforward. The retroauricular fascial flap can help to fix the wedge and provide good vascular supply to the grafted skin. The porous polyethylene wedge provides excellent projection for the reconstructed auricle.

Abstract

Eighty percent of nonsyndromic hearing losses are caused by autosomal-recessive (AR) inheritance, while most of the other 20% are caused by autosomal-dominant (AD) inheritance. Although AR nonsyndromic SNHL is most commonly caused by GJB2 and SLC26A4, there is no single gene that accounts for any significant proportion of AD SNHL. High-throughput sequencing techniques, also called next-generation sequencing (NGS) or massively parallel sequencing (MPS), may allow for routine definitive diagnosis of all possible genetic causes for hearing loss in the not-too-distant future.

Abstract

Laryngomalacia, the most common congenital anomaly of the infant airway, can lead to poor feeding and failure to thrive. The decision to perform the standard surgical treatment, supraglottoplasty, is often based upon a sustained period of poor weight gain or weight loss.To characterize patterns of growth in infants with laryngomalacia, preceding and following supraglottoplasty.Retrospective chart review. Bioinformatics techniques were used to procure data from a clinical data warehouse based on the HL7 Reference Information Model consisting of all infants who underwent supraglottoplasty from June 1, 2005 to October 31, 2013. Height and weight measurements were obtained from 76 operated patients allowing for characterization of growth changes from the time of surgery to an average of 9 months following surgery. Logistic regression analysis was performed to examine the following variables for correlations with changes in weight, height and body mass index percentiles: patient age at surgery, preoperative weight, gender, and ethnic background.Academic pediatric tertiary medical center.Patients under 2 years of age at the time of surgery, who underwent supraglottoplasty for laryngomalacia, with height and weight measurements recorded within 3 months preceding surgery and greater than 3 months following surgery.Supraglottoplasty.Change in weight, height and body mass index (BMI) percentile from pre-op to post-op.BMI increased from a mean of 15.4 to 18.0 and BMI percentile from a mean of 34 to 51 from pre-op to post-op. The largest BMI percentile increases were observed in infants that were 3 months or younger at the time of surgery, as well as in those under 12 months of age, who were in the lowest BMI quintile.Infants who underwent supraglottoplasty tended to be small in weight and stature, and gained weight after surgery. Most of the weight gain occurred within 6 months of surgery. The largest increases in BMI percentile were observed in infants who were younger and smaller at the time of surgery while the infants older than 18 months had no significant gain.

Abstract

To perform a systematic review of GJB2-associated hearing loss to describe genotype distributions and auditory phenotype.230 primary studies identified from Pubmed.Pubmed was searched systematically to screen broadly for any study reporting on genotype and carrier frequencies for biallelic GJB2-associated hearing loss in defined populations around the world. Genotype and audiometric data were extracted and subjected to meta-analysis to determine genotype distributions, carrier frequencies, rates of asymmetric or progressive hearing loss, and imaging abnormalities.A total of 216 articles comprising over 43,000 hearing-loss probands were included. The prevalence of biallelic GJB2-associated hearing loss was consistent across most of the 63 countries examined, with different mutations being predominant in different countries. Common mutations were found in greater than 3% of the general population worldwide. Meta-analysis of 48 case-control studies demonstrated a two-fold higher carrier frequency among hearing-impaired individuals compared to normal-hearing controls for truncating alleles, but not V37I. Progression, asymmetry, and imaging abnormalities were present in 14% to 19% of individuals with GJB2-associated hearing loss.GJB2 mutations are highly prevalent around the world. The multiple predominant mutations present in different populations attest to the importance of this gene for normal cochlear function and suggests an evolutionary heterozygote advantage. The unusually high carrier rate for truncating mutations among hearing-impaired individuals is consistent with either the presence of complementary mutations or a carrier phenotype. The significant rate of asymmetry and progression highlights the importance of diagnostic workup and close follow-up for this highly variable condition. Laryngoscope, 124:E34-E53, 2014.

Abstract

To describe a novel technique for removal of embedded distal airway foreign bodies with emphasis on procedural steps and management.The proximal bronchoplasty retrieval (PBR) technique is described including indications, rationale, surgical technique, and clinical decision making. Two representative cases are described in detail in order to demonstrate the technique.The PBR technique was successfully used to remove the two described embedded distal airway foreign bodies after other attempts had failed.Airway foreign bodies which have been present for several days or weeks are associated with edema and granulation tissue which often embeds the foreign body and may prevent removal due to proximal airway narrowing. We present a novel technique using endoscopic balloon dilation bronchoplasty to enlarge the airway proximal to the foreign body and enable removal with two example cases presented herein. The PBR technique allowed for removal of otherwise "stuck" distal airway foreign bodies.

Abstract

To perform a systematic review, comparing hearing outcomes of atresiaplasty versus osseointegrated bone conduction device (OBCD) in congenital aural atresia (CAA) patients.Approximately 107 studies, published from 1975 to 2012, evaluating hearing outcomes after atresiaplasty and/or OBCD in CAA patients were identified through a PubMed search.Articles that evaluated external auditory canal stenosis alone, did not report speech reception threshold (SRT), pure tone average (PTA), hearing gain, or air-bone gap (ABG) or had less than 5 patients were excluded. For authors or institutions with multiple reports, the largest or most recent study was included. Forty-one articles satisfied our inclusion and exclusion criteria.The number and percentage of ears with a postoperative SRT, PTA, ABG less than 30 dB, and/or average hearing gain were extracted. The total number of ears and the timing of the postoperative audiogram were also noted.Of the atresiaplasty ears, 73.8% (95% CI, 62.2%-85.4%), had a SRT less than 30 dB (338 ears), 60.3% (95% CI, 45.8%-74.8%) had a PTA less than 30 dB (390 ears), and 68.9% (95% CI, 59.4%-78.3%) had an ABG less than 30 dB (852 ears). The average hearing gain was 24.1 dB (95% CI, 21.62-26.51) for 516 ears. Hearing outcomes deteriorated with time. Of OBCD patients, 95.9% (95% CI, 91.5%-100.0%) had a PTA less than 30 dB (77 ears), and 98.2% (95% CI, 94.5%-100.0%) had an ABG less than 30 dB (47 ears); the average hearing gain was 38.0 dB (95% CI, 33.14-45.22) in 100 ears.The OBCD has better hearing outcomes compared with atresiaplasty in patients with CAA.

Abstract

IMPORTANCE Isotretinoin is frequently prescribed for the treatment of acne vulgaris. Among the numerous documented adverse effects, most common are xerostomia and cheilitis. Lip abscesses as a consequence of cheilitis present dramatically and may pose a diagnostic challenge. OBSERVATIONS We present a case of a 15-year-old boy with a severe lip abscess requiring incision and drainage and hospital admission for intravenous antibiotic treatment of methicillin-resistant Staphylococcus aureus. We discuss the pathophysiologic characteristics of isotretinoin therapy and the likely causative role that the medication played in the development of the lip abscess. CONCLUSIONS AND RELEVANCE Although rare, lip abscesses related to isotretinoin therapy present with substantial morbidity and should be promptly recognized. Misdiagnosis of mucositis and angioedema may delay appropriate therapy.

Abstract

Propranolol has recently emerged as an effective therapy for infantile hemangiomas causing regression. The ?-adrenergic receptor (AR) antagonist is thought to cause vasoconstriction by its effect on nitric oxide, block angiogenesis by its effect on vascular endothelial growth factor (VEGF), and induce apoptosis. In a prior report, we identified expression of ?2-AR (B2-AR) and its phosphorylated form (B2-ARP) in a case of infantile hemangioma that responded to propranolol treatment. We now explore the expression of ?ARs on a variety of vascular lesions utilizing a tissue microarray containing 141 lesions, including infantile hemangiomas, angiosarcomas, hemangiomas, hemangioendotheliomas, and various vascular malformations. The array was immunostained for B2-AR, B2-ARP, and ?3-AR (B3-AR), and the results scored for the intensity of endothelial cell expression as negative, weak positive, or strong positive. All phases of infantile hemangiomas had strong expression of all three receptors, with the exception of only weak expression of B2-ARP in the proliferative phase infantile hemangioma. Strong expression of all three receptors was present in many hemangiomas, hemangioendotheliomas, and vascular malformations. Absent to weak expression of all three receptors was seen in glomus tumor, hobnail hemangioendothelioma, pyogenic granuloma, and reactive vascular proliferations. This is the first study to report ?-AR expression in a variety of vascular lesions. Although immunohistochemical expression of the receptors does not necessarily indicate that similar pathways of responsiveness to ?-blockade are present, it does raises the possibility that ?-blockade could potentially affect apoptosis and decrease responsiveness to VEGF. Additional study is warranted, as therapeutic options are limited for some patients with these lesions.

Abstract

The platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important.This review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection.Platinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss.Collaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.

Abstract

Many guidelines for reporting hearing results use the threshold at 3 kilohertz (kHz), a frequency not measured routinely. This study assessed the validity of estimating the missing 3-kHz threshold by averaging the measured thresholds at 2 and 4 kHz. The estimated threshold was compared to the measured threshold at 3 kHz individually and when used in the pure-tone average (PTA) of 0.5, 1, 2, and 3 kHz in audiometric data from 2170 patients. The difference between the estimated and measured thresholds for 3 kHz was within ± 5 dB in 72% of audiograms, ± 10 dB in 91%, and within ± 20 dB in 99% (correlation coefficient r = 0.965). The difference between the PTA threshold using the estimated threshold compared with using the measured threshold at 3 kHz was within ± 5 dB in 99% of audiograms (r = 0.997). The estimated threshold accurately approximates the measured threshold at 3 kHz, especially when incorporated into the PTA.

Abstract

CH measurements can often be useful in the diagnosis of inner ear malformations associated with SNHL. Our aim was to establish the relationship between CH and age by using analysis of CT images in patients who underwent coronal CT scans of the temporal bone between 2001 and 2007.We measured CH on coronal CT scans of the temporal bone of 422 ears scanned from 2001 to 2007 in 211 patients, 1 month to 23 years of age. Using multivariate linear regression analysis, we determined the relationship of CH to age, sex, and HL type. In addition, 11 patients with multiple scans at different ages were assessed for change in CH with age.Average CH was 5.3 mm (normal range, 4.4-6.2 mm). Analysis showed no statistically significant change in CH across ages from 1 month to 23 years (95% CI for regression line slope = -0.003, 0.013). Likewise, there were no statistically significant differences in CH for patients with multiple scans at different ages. ICW increased with age as expected with increased cranial size. A small difference in CH between sexes was noted with males having greater CHs than females (P < .01). All patients with hypoplastic cochleas, defined by a CH <2 SDs from the mean (4.48 mm for males and 4.25 mm for females), had HL with a positive predictive value of 86%.CH does not change from 1 month of age to adulthood and is slightly greater in males than in females.

Abstract

To design a grading scale and audiologic protocols to better reflect clinical impact than the currently widely used classifications.Retrospective.Audiologic studies from 130 patients receiving cisplatin chemotherapy were analyzed. Pure-tone audiograms were evaluated using the newly proposed grading criteria, Brock criteria, and Common Terminology Criteria for Adverse Events (CTCAE). The resulting grades were then compared to recommended audiologic interventions. Auditory brainstem response (ABR) data and data on incidences of conductive hearing loss from other multi-institutional studies that the author participated in were compared to data from this cohort.Although the newly proposed, Brock, and CTCAE ototoxicity grades were significantly related to audiologist recommendations for assistive devices (P < .0001), the newly proposed criteria were more specific and allowed better delineation of different patients into distinct subgroups requiring either FM system (grade 2a) or hearing aid (grade 2b or higher). Multi-institutional data review indicated significant problems with ABR evaluations and separating out conductive hearing losses from ototoxicity.The newly proposed grading system needs to be paired with specific recommendations regarding audiologic monitoring protocols as well as active participation by the audiologists implementing the protocol to provide clinically accurate assessment and grading of ototoxicity.

Abstract

Diagnostic yield on GJB2 sequencing and computed tomography in the workup for idiopathic congenital sensorineural hearing loss is related to patient ethnicity.GJB2 sequencing and computed tomography of the temporal bones are important initial diagnostic tests in the workup of idiopathic congenital sensorineural hearing loss. Previous studies showed an association between mild or unilateral hearing loss and positive imaging findings and between severe or bilateral deafness and GJB2 mutations. Recent studies on connexin 26-associated deafness demonstrate a wide range of phenotypes that vary with ethnicity.We present a retrospective case series of 271 consecutive ethnically diverse patients evaluated for idiopathic congenital sensorineural hearing loss. Results of genetic testing and imaging were correlated with audiologic findings and ethnicity.All patients with asymmetric hearing loss had more positive findings on imaging. With respect to the severity of hearing loss, however, differences were noted between ethnic groups. Whereas white patients conformed to previous findings, Hispanics with severe hearing loss had similar rates of positive imaging and genetic testing results. Asians with mild hearing loss had significantly greater yield on genetic testing rather than on imaging. This reflects the high prevalence of the p.V37I mutation in GJB2 among Asians, which gives rise to a mild, frequently progressive phenotype.Ethnicity should be considered when determining the optimal sequence of diagnostic testing for idiopathic congenital sensorineural hearing loss. Asian patients, in particular, should all be screened for mutations in GJB2, especially in the case of mild hearing loss.

Abstract

(1) To present six patients with symptomatic airway hemangiomas treated with oral propranolol. (2) To review the diagnostic and treatment options for airway hemangiomas and propose a new management protocol.Retrospective review.Tertiary care children's hospital.Pediatric patients diagnosed with obstructive airway hemangiomas treated with oral propranolol. Patients were followed for symptomatic improvement and relief of airway obstruction on imaging or laryngoscopy.Seven patients presenting with airway obstruction were treated with propranolol. One patient had a focal hemangioma confined to the subglottis. Four patients had airway hemangiomas that extended beyond the confines of the larynx and trachea. A sixth patient had a bulky supraglottic hemangioma. A seventh patient with an extensive maxillofacial lesion failed propranolol therapy and was found to have a pyogenic granuloma on final pathology after excision. Six patients had failed standard medical therapy and/or surgical interventions and were treated successfully with oral propranolol with improvements in airway symptoms and oral intake, requiring no further surgical intervention. Treatment was initiated as early as 1.5 months of age, and as late as 22 months. No adverse side effects of propranolol were noted.Oral propranolol was successfully used to treat airway hemangiomas, resulting in rapid airway stabilization, obviating the need for operative intervention, and reducing the duration of systemic corticosteroid therapy while causing no obvious adverse effects. These outstanding results enable the possibility of use of a standardized diagnostic and treatment algorithm for airway hemangiomas that incorporates systemic propranolol.

Abstract

We present a new ototoxicity grading system that has clearly defined and frequency-specific audiometric criteria. The purpose of this study was to validate this grading system by assessing its correspondence to audiology treatment recommendations and comparing it with the currently utilized Common Terminology Criteria for Adverse Events (CTCAE).A retrospective chart review was conducted using audiologic, demographic, and clinical data from 134 children receiving 149 courses of chemotherapy consisting of cisplatin and/or carboplatin. Pure-tone audiograms were evaluated using both our proposed grading criteria and the CTCAE criteria. The resulting grades were then compared with charted audiologic interventions and a number of clinical parameters to assess the clinical validity of the grading scale.Chang grade 2a or higher predicted audiologic intervention. Although both the Chang and CTCAE ototoxicity grades were significantly related to audiologist recommendations for assistive devices such as hearing aids and/or frequency modulated systems (P < .0001), the Chang scale was more specific, with the CTCAE scale diverging from clinical recommendation at higher grades. As expected, patients receiving cisplatin had more severe hearing loss with concurrent carboplatin administration, radiation therapy exposure, younger age, smaller body-surface area, longer treatment exposure, and more severe disease.This grading system provides robust and clinically useful criteria to represent clinical hearing loss induced by ototoxicity with regard to the impact on speech and language and the need for assistive hearing devices. It is both more specific and more sensitive than the traditional CTCAE criteria for identifying clinically significant ototoxicity.

Abstract

To evaluate genotype-phenotype correlation over time for a cohort of children with connexin-26 (GJB2)-associated autosomal recessive hearing loss.Fifty-two children were identified from a database of individuals with homozygous or compound heterozygous mutations in GJB2 and subjected to chart review of their otolaryngologic and serial audiometric evaluations. Genotype-phenotype correlations were identified among the members of this group by appropriate statistical analyses.Hearing loss was most severe in individuals with two truncating mutations in GJB2 and mildest in those with two nontruncating mutations. Progressive hearing loss was seen directly by serial audiometry in 24% of all subjects, and suggested in a total of 28% when those with normal newborn hearing screens and subsequent hearing loss were included. Progression was particularly common among carriers of the p.V37I allele either in homozygosity or in compound heterozygosity with a truncating allele; these children are primarily of Asian descent and demonstrate mild, slowly progressive hearing loss.Phenotype in GJB2-associated hearing loss is correlated with genotype, with truncating mutations giving rise to more severe hearing loss. Progression of hearing loss is not uncommon, especially in association with the p.V37I allele. These results suggest that close audiometric follow-up is warranted for patients with GJB2-associated recessive hearing loss.

Abstract

An infant with a subglottic hemangioma remained in respiratory distress after multiple treatments failed and was found to have an enlarging mediastinal infantile hemangioma compressing the trachea. Treatment with oral propranolol resulted in resolution of symptoms within 2 days and a 50% reduction in lesion size within 1 week.

Abstract

The current study was conducted to determine whether amifostine is effective in reducing the toxicities associated with the administration of platinum-containing regimens in children with hepatoblastoma (HB).Patients were enrolled on P9645 beginning in March of 1999. Patients who had stage I/II disease received treatment with 4 cycles of combined cisplatin, 5-fluorouracil, and vincristine (C5V) with or without amifostine. Patients who had stage III/IV disease were randomized to receive treatment with 6 cycles of either C5V with or without amifostine or carboplatin alternating with cisplatin (CC) with or without amifostine. Patients who were randomized to receive amifostine were given a dose of 740 mg/m2 intravenously over 15 minutes before each administration of a platinum agent.Eighty-two patients were considered in a special interim analysis of the incidence of toxicity. The disease outcome for patients who received amifostine was similar to the outcome for patients who did not receive amifostine (P=.22). The incidence of significant hearing loss (>40 dB) was similar for patients who did or did not receive amifostine (38% [14 of 37 patients] vs 38% [17 of 45 patients], respectively; P=.68). There were no differences in the incidence of renal or bone marrow toxicities evaluated. Patients who received amifostine had a higher incidence of hypocalcemia (5% vs 0.5%; P=.00006).Amifostine in the doses and schedule used in this study failed to significantly reduce the incidence of platinum-induced toxicities in patients with HB.

Otorrhea in Infants With Tympanostomy Tubes Before and After Surgical Repair of a Cleft Palate23rd Annual Meeting of the American-Society-of-Pediatric-OtolaryngologyCurtin, G., Messner, A. H., Chang, K. W.AMER MEDICAL ASSOC.2009: 748?51

Abstract

To compare the incidence of otorrhea in a group of infants with cleft palate (CP) and tympanostomy tubes before and after surgical repair of the CP.Prospective observational study.Otolaryngology clinic at a tertiary care children's hospital.Thirty-three infants with CP and middle ear effusions who underwent tympanostomy tube placement. Subjects were observed from the time of tube placement until 6 months after CP repair.Incidence of otorrhea before and after CP repair.Subjects were observed a mean of 6.3 months before CP repair and 6 months after CP repair. Before CP repair, 11 of 33 infants (33%) had no episodes of otorrhea, compared with 22 of 33 (67%) after CP repair (P = .007). Fourteen infants (43%) had 2 or more episodes of otorrhea before CP repair compared with 2 (6%) after CP repair (P = .001). Before CP repair, significantly fewer tubes were patent at the time of the audiologic evaluation compared with after CP repair (39 of 62 [63%] vs 52 of 66 [79%]; P = .048). Average speech reception threshold for the infants with tympanostomy tubes before CP repair was 18.1 dB compared with 12.6 dB after CP repair (P = .01).The incidence of otorrhea after tympanostomy tube placement before CP repair is higher than the incidence after CP repair, although more than half of all infants (19 [58%]) had either 1 or no episodes of otorrhea before CP repair.

Abstract

We present a case of congenital salivary gland anlage tumor (SGAT) of the nasal septum in a 2-week-old infant who had difficulty breathing through her nose since birth. CT and MR imaging demonstrated a circumscribed mass within the nasal cavity that did not communicate with the intracranial compartment. Differential diagnosis and clinical significance of recognizing this rare lesion are reviewed.

Abstract

Examination of neonatal hearing screening practices around the world suggests that more attention is placed on infants who fail bilaterally on their hearing screen than infants who refer (fail) in one ear. Some programmes only report bilateral failures as positive hearing screens. This study investigates how limitations of the screening techniques demand continued audiologic evaluations in unilateral referrals.The study sample consisted of all infants born at a single academic paediatric hospital between February 1998 and February 2002.There were 16,007 infants screened using ALGO automated auditory brainstem response. Eighteen of the infants who failed the screen in one ear but passed in the other ear were found to have permanent hearing loss, and had their subsequent clinical course and audiologic management analysed. The final audiologic outcome after four years in both the pass and fail ear were examined.One group of unilateral referrals (n = 6) had obvious anatomic reasons for the ear failing the screen (canal atresia/stenosis). There were five patients in which the ear that passed the screen was later found on more extensive audiologic evaluation to have significant hearing loss. Review of recent literature was also completed to examine the methods by which unilateral screening referrals are commonly reported and whether or not this affected follow-up diagnostic evaluation.Infants who pass one ear and refer one ear on neonatal hearing screening still need to have thorough and prompt evaluations. In many cases, the ear that passed can be found to have significant hearing loss.

Abstract

To compare the postoperative recovery of patients who undergo intracapsular to subcapsular Coblation tonsillectomy.This was a prospective, randomized, double-blinded study. A total of 69 children, aged 2 to 16 years, were randomized to intracapsular (n = 34) or subcapsular (n = 35) tonsillectomy. The Coblation technique was used with both groups. Outcomes measures were assessed on postoperative day 1 or 2 and 5 or 6. These included child and parental rating of pain with the Wong Faces pain scale, analgesic use, oral intake, and activity level.Intracapsular tonsillectomy patients had similar levels of pain to subcapsular tonsillectomy patients on day 1 or 2. However, at day 5 or 6, intracapsular tonsillectomy patients had significantly less pain than the subcapsular tonsillectomy patients. Intracapsular patients ate more and were more active at both time points.Children with obstructive sleep apnea who undergo tonsillectomy demonstrate better postoperative recovery after intracapsular tonsillectomy. The intracapsular versus subcapsular difference may be best appreciated at a delayed time point (day 5 or 6) rather than early (day 1 or 2).

Abstract

To investigate whether normative inner ear measurements can assist in the evaluation of sensorineural hearing loss (SNHL).Retrospective cohort review.A tertiary care hospital.Computed tomography or magnetic resonance imaging was performed on 188 ears with SNHL and 220 ears without SNHL (204 children) between 2001 and 2004.Two readers measured the basal turn of cochlea (BTC) lumen, lateral semicircular canal (LSCC) bony island width, superior semicircular canal (SSCC) bony island width, and cochlear height (CH).A t test was performed comparing measurements in patients with and without SNHL. Interobserver variability was characterized by intraclass correlation coefficients and Bland-Altman plots.The t test results demonstrated no statistically significant differences between inner ear measurements in those with and without SNHL. The intraclass correlation coefficients for BTC lumen, CH, LSCC bony island width, and SSCC bony island width measurements was 0.612, 0.632, 0.869, and 0.912, respectively. Bland-Altman plots revealed systematic biases of 1%, 8%, 10%, and 21% for the BTC lumen, SSCC bony island width, LSCC bony island width, and CH measurements, respectively.Inner ear measurements in children with and without SNHL are not statistically different. Moreover, the measurements are difficult to interpret because while they demonstrate good reproducibility, they are susceptible to systematic biases. However, use of inner ear measurements is more sensitive in identifying vestibulocochlear dysplasias and should be considered to complement visual analysis.

Two patients with the V371/235delC genotype: Are radiographic cochlear anomalies part of the phenotype?INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGYSchrijver, I., Chang, K. W.2006; 70 (12): 2109-2113

Abstract

We present two East Asian patients with sensorineural hearing loss (SNHL) and compound heterozygosity for the 235delC and V37I mutations in the GJB2 gene. One patient has a unilaterally enlarged vestibular aqueduct, which underscores the importance of routine CT examination in children with SNHL, even if GJB2 (connexin 26) mutations have been identified. The second patient was not available for evaluation by CT. The pathogenic role of the V37I mutation has been controversial. We review the literature and present evidence in support of pathogenicity. Larger studies in compound heterozygous individuals and co-transfection studies will allow better genotype-phenotype correlations and prognostication.

Abstract

Foreign-body aspiration is a common cause of respiratory distress among children. Here we describe an 8-month-old, previously 34-week premature, male patient who presented with a 1-day history of fever and increased work of breathing. Of note, 3 weeks before presentation, the patient had been treated with orally administered amoxicillin for presumed pneumonia and exhibited good clinical response. No chest radiograph was obtained at that time. A current chest radiograph revealed hyperexpansion of the left lung, with a mediastinal shift. Although the patient was referred because of possible foreign-body aspiration, no clear history of an aspiration event was obtained, and computed tomographic scans of the chest were recommended. These showed extensive hilar and mediastinal lymphadenopathy, resulting in obstruction of the left bronchus. Bronchoscopy revealed a cheesy granulomatous mass in the left mainstem bronchus, which was ball-valving into the upper bronchus. Removal resulted in improvement of the patient's respiratory status. Pathology, bronchial lavage, and gastric aspirate specimens all revealed acid-fast bacilli, consistent with Mycobacterium tuberculosis infection. This unusual presentation of tuberculosis may become more common in the United States as the incidence of immigrants carrying tuberculosis increases.

Abstract

To compare the postoperative recovery of patients receiving Coblation-assisted (Arthrocare, Sunnyvale, CA) intracapsular tonsillectomy with that of patients receiving traditional subcapsular electrocautery tonsillectomy.This was a prospective, randomized, double-blinded, controlled study. One hundred one children, aged 2 to 16 years, were randomized to Coblation or to conventional electrocautery tonsillectomy. Only patients with the operative indication of obstructive sleep apnea were entered into the study. Intracapsular tonsillectomy was performed on the Coblation group, and traditional subcapsular dissection was performed on the electrocautery group. Adenoidectomy was performed with the curette in both groups. Outcome measures were assessed on days 1, 3, and 5 after surgery. These included child and parental rating of pain by using the Wong Faces pain scale, analgesic use, oral intake, and activity level. Patients, parents, and the nurse practitioner obtaining the outcome data were blinded to treatment arm.Treatment groups were similar in age, gender, and weight. Surgical time and estimated blood loss were similar. There were no complications in either group. Coblation patients had less pain and greater oral intake at all 3 time points. Percentage of normal activity level returned to >70% earlier and more frequently in Coblation patients. There was slightly decreased analgesic use on postoperative day 5 in the Coblation group.Children with obstructive sleep apnea undergoing tonsillectomy and adenoidectomy demonstrate significantly better postoperative recovery after Coblation-assisted intracapsular tonsillectomy.

Abstract

Transtympanic administration of the antioxidant N-acetylcysteine or lactated Ringer's solution onto the round window membrane will prevent cisplatin ototoxicity in the guinea pig model.Cochlear ototoxicity is a well-known side effect of cisplatin administration, with the mechanism of injury thought to rest in oxidative damage to the outer hair cells. However, previous attempts at transtympanic antioxidant delivery have met with varied success. We present an effective method of counteracting cisplatin ototoxicity via the transtympanic application of lactated Ringer's solution or N-acetylcysteine.Baseline distortion product otoacoustic emission measurements were obtained. Intraperitoneal cisplatin was administered to a cumulative dose of 20 mg/kg. The middle ears were either untreated (control) or filled with normal saline (negative control), 2%N-acetylcysteine diluted in normal saline (treatment), or lactated Ringer's solution (treatment) via anterosuperior quadrant myringotomies. Posttreatment distortion product otoacoustic emissions were obtained.Animals in the untreated control group and the negative control normal saline group demonstrated consistent obliteration of distortion product otoacoustic emissions. However, those receiving either lactated Ringer's solution or 2%N-acetylcysteine diluted in normal saline demonstrated significant preservation of distortion product otoacoustic emissions. The treatment regimen was well tolerated, with minimal animal loss.We have demonstrated the efficacy of transtympanic lactated Ringer's solution and N-acetylcysteine in the prevention of cisplatin ototoxicity using a guinea pig model. The possible mechanisms for the high efficacy of lactated Ringer's solution are discussed in detail.

A randomized study of platinum-based chemotherapy with or without amifostine for the treatment of children with hepatoblastoma: A report of the Intergroup Hepatoblastoma Study P9645.Proc Am Soc Clin OncolKatzenstein HM, Chang K, Krailo M, et al2004; 22: 8518

Abstract

Pediatric resident physicians' clinical diagnostic accuracy of otitis media is unknown. We attempted to correlate the clinical examination of pediatric house staff with pediatric otolaryngologists and tympanometry.Pediatric residents evaluated patients who were scheduled in the pediatric acute care clinic and completed a provider examination form detailing their otoscopic findings, interpretation, and treatment plan. Patients were then immediately reevaluated by a pediatric otolaryngologist using an identical form. Tympanometry was also performed by a pediatric audiologist. We used kappa statistics to calculate correlation of clinical findings and interpretation.A total of 103 patients consented for the study; 70 patients were examined by 27 different pediatric residents with 43 patients (86 ears) examined by all 3 providers. Correlation of clinical findings between all pediatric residents and the pediatric otolaryngologists was a kappa statistic of 0.30 (fair agreement). The individual diagnostic finding with the greatest correlation was tympanic membrane erythema (kappa statistic: 0.40 [fair agreement]), and the worst correlate was tympanic membrane position (kappa statistic: 0.16 [slight agreement]). Resident interpretation and tympanometry yielded a kappa statistic of 0.20 (slight agreement), and the otolaryngologist interpretation and tympanometry yielded a kappa statistic of 0.32 (fair agreement).Otitis media is the most common disease seen by practicing general pediatricians, but there is a paucity of formalized resident education. We demonstrated only a slight to moderate correlation between the clinical diagnostic examinations of pediatric residents and pediatric otolaryngologists and tympanometry.

Abstract

Distortion product otoacoustic emissions (DPOAE) were measured serially in guinea pigs before and following 4-h exposures to a half-octave band of noise centered at 6 kHz. Stimulus parameters used to elicit the DPOAE were f2/f1 = 1.26 and L2 = L1-10. The 80 dB SPL exposures resulted in attenuation of emissions, which was maximal at the frequency one-half octave above the exposure when referenced to the f2 stimulus, and which recovered back to baseline after 2 days. The 90 dB SPL exposures resulted in a permanent deficit in emissions elicited by high-frequency stimuli, as measured after 8 days of recovery. A statistically significant difference was also found between animals exposed continuously for 4 h versus animals given two 2-h exposures separated by a 1-h break. Measures of f2-f1 and 3f1-2f2 indicated that they were more sensitive than 2f1-f2 to alterations in cochlear function after noise exposure.

Abstract

Death following pediatric tonsillectomy is very rare. If deaths occur, they are most commonly due to bleeding or aspiration. In this presentation, we would like to illustrate another potentially lethal complication following the pediatric tonsillectomy, iatrogenic hyponatremia. We have encountered 3 patients who have developed post-operative hyponatremia. This has resulted in 2 deaths. The third patient was successfully treated and developed no permanent sequela. We will discuss the etiology and pathophysiology of post-operative hyponatremia including guidelines for administering fluid and electrolytes intra-operatively and post-operatively. We expect that fatal post-operative hyponatremia can be avoided in the pediatric tonsillectomy patients.

Abstract

Screening auditory status prior to neonatal hospital discharge to identify newborns with severe hearing impairment is an important pediatric care priority. Evoked otoacoustic emission (OAE) testing is a quick noninvasive method. The purpose of this study was to determine the relationship between external auditory canal and middle ear status with click-evoked OAE. It was hypothesized that vernix caseosa, debris in the ear canal, and middle ear fluid contribute to the OAE fail rate.All neonates had an initial OAE examination. A second investigator, "blinded" to the results, examined all ears otoscopically, cleaned any obstructing debris, and repeated with a second OAE test.All neonates were tested in a designated nursery at a mean age of 43 +/- 21 hours.Forty-one full-term neonates were prospectively enrolled.The ear canals with debris were cleaned under direct vision with a pediatric swab dampened by an alcohol wipe.The primary outcome measure was the postcleaning OAE pass rate.The preotoscopic examination pass rate of 82 ears was 76%. The OAE pass rate improved to 91% after debris removal.The results indicate that the examination and cleaning of the external ear canal are important components of the neonatal screening process.

Abstract

We present two siblings with severe laryngomalacia requiring surgical intervention during the newborn period, microcephaly, developmental delay, cleft palate, preaxial polydactyly, dysplastic nails and conductive hearing loss (persistent after tympanostomy tube placement). In addition the girl has microopthalmia and the boy was born with a patent ductus arteriosus, mild pelviectasis, and hypospadias. This combination of multiple congenital anomalies has not been described previously and may represent a previously undescribed syndrome with autosomal inheritance.